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Synthesis of a novel polycyclic ring scaffold with antimitotic properties via a selective domino Heck–Suzuki reaction† †Electronic supplementary information (ESI) available: Full experimental details, 1H and 13C NMR spectra and X-ray crystallographic data for compound 4d. CCDC 936207. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4sc02547d Click here for additional data file. Click here for additional data file

Authors :
Alza, Esther
Laraia, Luca
Ibbeson, Brett M.
Collins, Súil
Galloway, Warren R. J. D.
Stokes, Jamie E.
Venkitaraman, Ashok R.
Spring, David R.
Source :
Chemical Science
Publication Year :
2014
Publisher :
Royal Society of Chemistry, 2014.

Abstract

The synthesis of a previously undescribed sp3-rich 6-5-5-6 tetracyclic ring scaffold using a palladium catalysed domino Heck–Suzuki reaction is reported.<br />The synthesis of a previously undescribed sp3-rich 6-5-5-6 tetracyclic ring scaffold using a palladium catalysed domino Heck–Suzuki reaction is reported. This reaction is high-yielding, selective for the domino process over the direct Suzuki reaction and tolerant towards a variety of boronic acids. The novel scaffold can also be accessed via domino Heck–Stille and radical cyclisations. Compounds based around this scaffold were found to be effective antimitotic agents in a human cancer cell line. Detailed phenotypic profiling showed that the compounds affected the congression of chromosomes to give mitotic arrest and apoptotic cell death. Thus, a novel structural class of antimitotic agents that does not disrupt the tubulin network has been identified.

Subjects

Subjects :
Chemistry

Details

Language :
English
ISSN :
20416539 and 20416520
Volume :
6
Issue :
1
Database :
OpenAIRE
Journal :
Chemical Science
Accession number :
edsair.pmid..........d8bbd2ccc08aba3ca65e2cd742b8b559